Tyrosinase is the rate-limiting enzyme in the melanogenesis process. It remains the most efficient way to downregulate melanin production and improve unsightly pigmentary disorders. The aim of our investigations was to find a structurally characterized molecule with better efficacy than existing molecules without cell toxicity. We focused our investigations on compounds that could act as substrate-mimicking inhibitors of tyrosinase and identified N-feruloyldopamine as the best candidate. In vitro, N-feruloyldopamine inhibited human tyrosinase with higher efficacy than the reference inhibitor arbutin without cell toxicity at least up to 100 μM as measured in cultured normal human epidermal melanocytes (NHEMs). Moreover, the inhibition appeared to be specific to mammalian tyrosinases as shown by a very poor inhibition of mushroom tyrosinase, but a significant decrease of total melanin in B16-F10 cells. The antioxidant capacity assessed using DPPH (1,1-diphenyl-2-picrylhydrazyl) assay was comparable to that of vitamin C and finally, N-feruloyldopamine exerted a significant inhibition of Pmel17 gene expression when used at 100 μM on cultured NHEM. Taken together, these results suggest that N-feruloyldopamine is a serious candidate for in vivo application as complexion-brightening ingredient.
